We propose to build on the successes of our of past COBRE phase I and II grants to create a collection of three research cores that, coupled with a pilot project mechanism, will provide us with the resources to develop a strong team of investigators to study the prevention and treatment of osteoarthritis. Ours is a multidisciplinary, multi-scale approach to the study of osteoarthritis (OA), involving faculty doing work in extracellular matrix proteins, biomechanical modeling of joint forces, and clinical studies. The uniqueness of our approach will be the examination of OA from the integrated perspectives of tissue mechanics, biomechanics, and rehabilitation. We will build on the distinctive organization of the center established with the COBRE award and the collaborative projects described in this application. Three core resources will be run through this award: (1) A cytomechanics core, first established in our phase II grant, will be strengthened to provide tools for orthopaedic researchers to study how bone, cartilage and ligament respond to stress and strain. This involves tools for bioimaging and micromechanical testing. (2) A patient specific modeling (PSM) core will be established. This is a modification and expansion of the motion analysis core established in our COBRE I award. It will provide a means to determine differences in tissue forces associated with pathologies and will also be used to determine biomechanical differences associated with various treatment paths, which may impact the development of osteoarthritis. (3) A clinical research core (the ResCore) will be established for the first time to aid us as we expand our clinical trials. It will provide patient database access and biostatistics support for al projects. In addition, we will continue to maintain our mentoring mechanism. Faculty development is key to our success and we will continue to mentor our faculty and work with our External Advisory Committee to provide very regular feedback to COBRE investigators about their research. Our goal is to use these resources to establish a large base of NIH R01 funded investigators studying osteoarthritis and, by those R01 grants, be able to support our cores in the future and greatly expand our efforts to make strong progress in understanding the prevention and treatment of OA.